Two National Institutes of Health (NIH)-supported studies of an experimental malaria vaccine in healthy adults in Mali found that all three treatment regimens tested were safe. One of the studies enrolled 300 healthy women ages 18 to 38 who planned to become pregnant soon after vaccination. This study began with drug treatment to remove the malaria parasites, followed by three injections one month apart with either a saline placebo or the investigational vaccine at one of two doses. Both doses of the vaccine candidate provided significant protection against parasite infections and clinical malaria that lasted for two years without the need for a booster dose—a first for a malaria vaccine. In an exploratory analysis of women who became pregnant during the study, the vaccine significantly protected them against malaria in pregnancy. If confirmed by further clinical trials, the approach modelled in this study could provide improved opportunities for preventing malaria in pregnancy.

Spread by Anopheles mosquitoes, malaria parasites, including those of the species Plasmodium falciparum (Pf) can cause disease in people of all ages, but pregnant women, infants, and young children are particularly vulnerable to life-threatening disease. Malaria parasitemia during pregnancy is estimated to result in up to 50,000 maternal deaths and 200,000 stillbirths in Africa each year.

The studies were jointly led by researchers from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and the University of Sciences, Techniques and Technologies, Bamako (USTTB), Mali. The investigational vaccine used in both studies was PfSPZ Vaccine, a radiation-attenuated vaccine based on Pf Sporozoites (a stage in the parasite’s life cycle) manufactured by Sanaria Inc., Rockville, Maryland. Several previous clinical trials of the PfSPZ vaccine have shown it to be safe, including in countries where malaria is endemic, such as Mali. For example, results published in 2022 from an NIAID-sponsored, placebo-controlled trial of a three-dose regimen of the PfSPZ vaccine in Burkina Faso found that the vaccine had efficacy of up to 46% that lasted for at least 18 months.

During the first year of the current study, 55 women became pregnant within 24 weeks of the third dose of vaccine. Among these women, vaccine effectiveness against parasite infestation (whether before or during pregnancy) was 65% in those who received the lower dose vaccine and 86% in those who received the higher dose. Among the 155 women who became pregnant during both years of the study, vaccine effectiveness was 57% in those who received the lower dose vaccine and 49% in those who received the higher dose vaccine.

Women who received the investigational vaccine at either dose became pregnant earlier than women who received a placebo, although this finding was not statistically significant, the researchers reported. The researchers speculate that the PfSPZ vaccine may prevent malaria-related early pregnancy losses because the risk of parasite infection during the periconception period was reduced by 65 to 86%.

“Preconception vaccination is a new strategy to reduce mortality in women with malaria during pregnancy.“, the researchers note. They plan to study the safety of PfSPZ vaccine given during pregnancy and then to test the effectiveness of PfSPZ before conception or during pregnancy in larger clinical trials.”Existing measures do not protect pregnant women from malaria,” they added. “A safe and effective vaccine is urgently needed and our results suggest that the PfSPZ vaccine may be a suitable candidate.“, they conclude.

The PfSPZ vaccine study team was led by Alassane Dicko, MD, of the Malaria Research and Training Center (MRTC), USTTB, Mali, Stephen L. Hoffman, MD, of Sanaria Inc., and Patrick E. Duffy, MD, of the NIAID Laboratory of Malaria Immunology and Vaccinology. Joint first authors were Halimatou Diawara, MD, of the MRTC, and Sara A. Healy, MD, NIAID.